Reversal of Blimp-1-mediated apoptosis by A1, a member of the Bcl-2 family

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Blimp-1 (B lymphocyte-induced maturation protein 1) is strongly expressed during the late stages of B cell differentiation to immunoglobulin-secreting plasma cells. Overexpression of Blimp-1 in B lymphoma cells has been reported to induce either growth arrest and cell death or Ig secretion and terminal differentiation, depending on the developmental stage of the recipient lymphomas. By using a retroviral expression system we show that Blimp-1-transduced immature WEHI 231 murine B lymphoma cells produce J chain, increased levels of the secretory form of micro heavy chain mRNA and secrete IgM for a short period of time. Concomitantly, they exhibit altered ratios of c-myc/mad4 mRNA levels, a reduction in the expression of the anti-apoptotic bcl-2 family member A1 and a distinct growth disadvantage, followed by cell death. Reintroduction of A1 by retroviral transduction greatly extends the life span of Blimp-1-expressing WEHI 231 cells which continue to secrete IgM. These data suggest that levels of A1 may determine the checkpoint between death and survival of Blimp-1-expressing B cells at different stages of differentiation.

Details

OriginalspracheEnglisch
Seiten (von - bis)2988-98
Seitenumfang11
FachzeitschriftEuropean Journal of Immunology
Jahrgang29
Ausgabenummer9
PublikationsstatusVeröffentlicht - Sept. 1999
Peer-Review-StatusJa

Externe IDs

Scopus 0343340028
ORCID /0000-0002-0320-4223/work/150884988

Schlagworte

Schlagwörter

  • Animals, Apoptosis/immunology, Cell Differentiation, Cell Survival/genetics, Cells, Cultured, DNA-Binding Proteins/genetics, Down-Regulation, Gene Transfer Techniques, Genetic Vectors, Homeodomain Proteins, Humans, Immunoglobulin J-Chains/metabolism, Lymphoma, B-Cell, Mice, Minor Histocompatibility Antigens, Phenotype, Positive Regulatory Domain I-Binding Factor 1, Proto-Oncogene Proteins c-bcl-2/genetics, Replication Protein C, Repressor Proteins, Saccharomyces cerevisiae Proteins, Transcription Factors/genetics, Tumor Cells, Cultured